Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - kaftrio

Document Subject

Generated Narrative: MedicinalProductDefinition mp9907a30e9752c1b71142c1d64ee9aa50

identifier: http://ema.europa.eu/identifier/EU/1/20/1468/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

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part: nan

type: Strength part

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part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-9907a30e9752c1b71142c1d64ee9aa50

identifier: http://ema.europa.eu/identifier/EU/1/20/1468/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - kaftrio

Attesters

What is in this leaflet

1. What Kaftrio is and what it is used for
2. What you need to know before you take Kaftrio
3. How to take Kaftrio
4. Possible side effects
5. How to store Kaftrio
6. Contents of the pack and other information

Kaftrio contains three active substances: ivacaftor, tezacaftor and elexacaftor. The medicine helps lung cells to work better in some patients with cystic fibrosis (CF). CF is an inherited condition in which the lungs and the digestive system can become clogged with thick, sticky mucus.

Kaftrio taken with ivacaftor is for patients aged 6 years and over who have CF, with at least one F508del mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Kaftrio is intended as a long-term treatment.

Kaftrio works on a protein called CFTR. The protein is damaged in some people with CF, if they have a mutation in the CFTR gene.

Kaftrio is normally taken with another medicine, ivacaftor. Ivacaftor causes the protein to work better, while tezacaftor and elexacaftor increase the amount of protein at the cell surface.

Kaftrio (taken with ivacaftor) helps your breathing by improving your lung function. You may also notice that you do not get ill as often, or that it is easier to gain weight.

Do not take Kaftrio:

• If you are allergic to ivacaftor, tezacaftor, elexacaftor, or any other ingredients of this medicine (listed in section 6). Talk to your doctor and do not take the tablets, if this applies to you. Warnings and precautions

• Talk to your doctor if you have liver problems, or have had them previously. Your doctor may need to adjust your dose.

• Your doctor will do some blood tests to check your liver before and during treatment with Kaftrio, especially if your blood tests showed high liver enzymes in the past. Liver enzymes in the blood can increase in patients receiving Kaftrio.

Tell your doctor right away if you have any symptoms of liver problems. These are listed in section 4. * Depression (including suicidal thoughts and behaviours) has been reported in patients while taking Kaftrio, usually starting within the first three months of treatment. Talk to your doctor straight away if you (or someone taking this medicine) experience any of the following symptoms which may be signs of depression: sad or altered mood, anxiety, feelings of emotional discomfort or thoughts of harming or killing yourself.

• Talk to your doctor if you have kidney problems, or you have previously had them.

• Talk to your doctor before starting treatment with Kaftrio if you have received an organ transplant.

• Talk to your doctor if you are using hormonal contraception for example, women using the contraceptive pill. This may mean you are more likely to get a rash while taking Kaftrio.

• Your doctor may do eye examinations before and during treatment with Kaftrio. Cloudiness of the eye lens (cataract) without any effect on vision has occurred in some children and adolescents receiving this treatment.

Children under 6 Do not give this medicine to children under the age of 6 years because it is not known if Kaftrio is safe and effective in this age group.

Other medicines and Kaftrio Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines can affect how Kaftrio works or may make side effects more likely. In particular, tell your doctor if you take any of the medicines listed below. Your doctor may change the dose of one of the medicines if you take any of these.

• Antifungal medicines (used for the treatment of fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole and voriconazole.
• Antibiotic medicines (used for the treatment of bacterial infections). These include clarithromycin, erythromycin, rifampicin, rifabutin and telithromycin.
• Epilepsy medicines (used for the treatment of epileptic seizures or fits). These include carbamazepine, phenobarbital and phenytoin.
• Herbal medicines. These include St. John s wort (Hypericum perforatum).
• Immunosuppressants (used after an organ transplantation). These include ciclosporin, everolimus, sirolimus and tacrolimus.
• Cardiac glycosides (used for the treatment of some heart conditions). These include digoxin.
• Anticoagulant medicines (used to prevent blood clots). These include warfarin.
• Medicines for diabetes. These include glimepiride, glipizide, glyburide, nateglinide and repaglinide.
• Medicines for lowering blood cholesterol. These include pitavastatin and rosuvastatin.
• Medicines for lowering blood pressure. These include verapamil.

Kaftrio with food and drink Avoid food or drinks containing grapefruit during treatment as these may increase the side effects of Kaftrio by increasing the amount of Kaftrio in your body.

Pregnancy and breast-feeding

• Ask your doctor for advice before taking this medicine if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby.
• Pregnancy: It may be better to avoid using this medicine during pregnancy. Your doctor will help you decide what is best for you and your child.
• Breast-feeding: It is not known if ivacaftor, tezacaftor or elexacaftor passes into breast milk. Your doctor will consider the benefit of breast-feeding for your baby and the benefit of treatment for you to help you decide whether to stop breast-feeding or to stop treatment.

Driving and using machines Kaftrio can make you dizzy. If you feel dizzy, do not drive, cycle, or use machines unless you are not affected.

Kaftrio contains sodium This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free .

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor will determine the correct dose for you.

Kaftrio is usually taken with ivacaftor.

Recommended dose for patients aged 6 years and over Age Weight Morning dose Evening dose 6 to < 12 years <30 kg Two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg tablets One ivacaftor 75 mg tablet 6 to < 12 years 30 kg Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets One ivacaftor 150 mg tablet 12 years and older

• Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets One ivacaftor 150 mg tablet

Take the morning and evening tablets about 12 hours apart.

The tablets are for oral use.

Take both Kaftrio and ivacaftor tablets with food that contains fat. Meals or snacks that contain fat include those prepared with butter or oils or those containing eggs. Other fat-containing foods are:

• Cheese, whole milk, whole milk dairy products, yogurt, chocolate
• Meats, oily fish
• Avocados, hummus, soy-based products (tofu)
• Nuts, fat-containing nutritional bars or drinks

Avoid food and drink containing grapefruit while you are taking Kaftrio. See Kaftrio with food and drink in section 2 for more details.

Swallow the tablets whole. Do not chew, crush or break the tablets before swallowing.

You must keep using all your other medicines, unless your doctor tells you to stop.

If you have liver problems, either moderate or severe, your doctor may reduce the dose of your tablets or decide to stop treatment with Kaftrio. See also Warnings and precautions in section 2. If you take more Kaftrio than you should Contact your doctor or pharmacist for advice. If possible, take your medicine and this leaflet with you. You may get side effects, including those mentioned in section 4 below.

If you forget to take Kaftrio If you forget a dose, work out how long it is since the dose you missed.

• If less than 6 hours have passed since you missed a dose, either morning or evening, take the forgotten tablet(s) as soon as possible. Then go back to your usual schedule.
• If more than 6 hours have passed:
• If you missed a morning dose of Kaftrio, take it as soon as you remember. Do not take the evening dose of ivacaftor. Take the next morning dose at the usual time.
• If you missed an evening dose of ivacaftor, do not take the missed dose. Wait for the next day and take the morning dose of Kaftrio tablets as usual. Do not take a double dose to make up for any missed tablets.

If you stop taking Kaftrio Your doctor will tell you how long you need to keep taking Kaftrio. It is important to take this medicine regularly. Do not make changes unless your doctor tells you.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects Possible signs of liver problems Liver damage and worsening of liver function in people with severe liver disease. The worsening of liver function can be serious and may require transplantation.
Increased liver enzymes in the blood are common in patients with CF. These may be signs of liver problems:

• Pain or discomfort in the upper right area of the stomach (abdominal) area
• Yellowing of the skin or the white part of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark urine

Depression. Signs of this include sad or altered mood, anxiety, feelings of emotional discomfort.

Tell your doctor straight away if you have any of these symptoms.

Very common side effects (may affect more than 1 in 10 people)

• Rash (more common in women than in men) Tell your doctor straight away if you notice a rash.

Other side effects seen with Kaftrio: Very common (may affect more than 1 in 10 people)

• Headache
• Dizziness
• Upper respiratory tract infection (common cold)
• Oropharyngeal pain (sore throat)
• Nasal congestion
• Stomach or abdominal pain
• Diarrhoea
• Increased liver enzymes (signs of stress on the liver)
• Changes in the type of bacteria in mucus

Common (may affect up to 1 in 10 people)

• Flu
• Abnormal breathing (Shortness of breath or difficulty breathing)
• Low blood sugar (hypoglycaemia)
• Runny nose
• Sinus problems (sinus congestion)
• Redness or soreness in the throat
• Ear problems: ear pain or discomfort, ringing in the ears, inflamed eardrum
• Spinning sensation (inner ear disorder)
• Wind (flatulence)
• Spots (acne)
• Itchy skin
• Breast mass
• Feeling nauseous
• Increased creatine phosphokinase (sign of muscle breakdown) seen in blood tests

Uncommon (may affect up to 1 in 100 people)

• Breast and nipple problems: inflammation, pain
• Enlargement of the breast in men
• Increases in blood pressure
• Wheezing
• Blocked ears (ear congestion)

Not known (frequency cannot be estimated from the available data)

• Damage to the liver (liver injury)
• Raised bilirubin measurement (liver blood test)

Additional side effects in adolescents Side effects in adolescents are similar to those observed in adults.

Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the outer carton and on the blister after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

What Kaftrio contains

• The active substances are ivacaftor, tezacaftor and elexacaftor.

Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets Each film-coated tablet contains 37.5 mg of ivacaftor, 25 mg of tezacaftor and 50 mg elexacaftor.

Kaftrio 75 mg/50 mg/100 mg film-coated tablets
Each film-coated tablet contains 75 mg of ivacaftor, 50 mg of tezacaftor and 100 mg elexacaftor.

• The other ingredients are:

Tablet core: Hypromellose (E464), hypromellose acetate succinate, sodium laurilsulfate (E487), croscarmellose sodium (E468), microcrystalline cellulose (E460(i)), and magnesium stearate (E470b).

Tablet film coating: Hypromellose (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), talc (E553b), iron oxide yellow (E172), and iron oxide red (E172).

See the end of section 2 for important information about the contents of Kaftrio.

What Kaftrio looks like and contents of the pack Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets are light orange, capsule-shaped tablets stamped with T50 on one side and plain on the other.

Kaftrio 75 mg/50 mg/100 mg film-coated tablets are orange, capsule-shaped tablets stamped with T100 on one side and plain on the other.

Kaftrio is available in pack size of 56 tablets (4 blister cards, each with 14 tablets).

Marketing Authorisation Holder Vertex Pharmaceuticals (Ireland) Limited Unit 49, Block F2, Northwood Court, Santry,
Dublin 9, D09 T665,
Ireland Tel: +353 (0)1 761 7Manufacturer Almac Pharma Services (Ireland) Limited Finnabair Industrial Estate Dundalk Co. Louth A91 P9KD Ireland

Almac Pharma Services Limited Seagoe Industrial Estate Craigavon Northern Ireland BT63 5UA United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien, , esk
republika, Danmark, Deutschland, Eesti, France, Hrvatska, Ireland, sland, , Latvija, Lietuva, Luxembourg/Luxemburg, Magyarorsz g, Malta, Nederland, Norge, sterreich, Polska, Portugal, Rom nia, Slovenija, Slovensk republika, Suomi/Finland, Sverige, United Kingdom (Northern Ireland) Vertex Pharmaceuticals (Ireland) Limited T l/Tel/Te /Tlf/S mi/ /Puh:
+353 (0) 1 761 7Espa a Vertex Pharmaceuticals Spain, S.L. Tel: + 34 91 7892
Vertex

: +30 (211) 2120Italia Vertex Pharmaceuticals (Italy) S.r.l. Tel: +39 0697794This leaflet was last revised in

Other sources of information Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

Package leaflet: Information for the patient

Kaftrio 60 mg/40 mg/80 mg granules in sachet
Kaftrio 75 mg/50 mg/100 mg granules in sachet ivacaftor/tezacaftor/elexacaftor

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before your child starts taking this medicine because it contains important information for your child.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your child s doctor or pharmacist.
• This medicine has been prescribed for your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as your child.
• If you get any side effects, talk to your child s doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.